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摘要:
N-methyl-D-aspartate receptors(NMDARs) are a family of ionotropic glutamate receptors mainly known to mediate excitatory synaptic transmission and plasticity. Interestingly, low-dose NMDAR antagonists lead to increased, instead of decreased, functional connectivity;and they could cause schizophrenia-and/or antidepressant-like behavior in both humans and rodents. In addition, human genetic evidences indicate that NMDAR loss of function mutations underlie certain forms of epilepsy, a disease featured with abnormal brain hyperactivity. Together, they all suggest that under certain conditions,NMDAR activation actually lead to inhibition, but not excitation,of the global neuronal network. Apparently, these phenomena are rather counterintuitive to the receptor’s basic role in mediating excitatory synaptic transmission. How could it happen? Recently, this has become a crucial question in order to fully understand the complexity of NMDAR function, particularly in disease. Over the past decades, different theories have been proposed to address this question. These include theories of 'NMDARs on inhibitory neurons are more sensitive to antagonism', or 'basal NMDAR activity actually inhibits excitatory synapse', etc. Our review summarizes these efforts, and also provides an introduction of NMDARs,inhibitory neurons, and their relationships with the related diseases.Advances in the development of novel NMDAR pharmacological tools, particularly positive allosteric modulators, are also included to provide insights into potential intervention strategies.
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篇名 How could N-methyl-D-aspartate receptor antagonists lead to excitation instead of inhibition?
来源期刊 临床转化神经医学(英文版) 学科 医学
关键词 N-METHYL-D-ASPARTATE receptor SYNAPTIC transmission INHIBITION EXCITATION brain disease positive ALLOSTERIC modulator
年,卷(期) 2018,(2) 所属期刊栏目
研究方向 页码范围 73-98
页数 26页 分类号 R741
字数 语种
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节点文献
N-METHYL-D-ASPARTATE
receptor
SYNAPTIC
transmission
INHIBITION
EXCITATION
brain
disease
positive
ALLOSTERIC
modulator
研究起点
研究来源
研究分支
研究去脉
引文网络交叉学科
相关学者/机构
期刊影响力
神经科学(英文)
季刊
2096-5958
10-1534/R
Xueyuan Building Tsi
出版文献量(篇)
176
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0
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0
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